This proposal addresses the problem of renewal of photoreceptor outer segments, a major theme in eye research of the past decade. It is based on the idea that a more complete understanding of the control of disk addition may lead to insights into the nature of membrane biogenesis in general, and to a better understanding of how specific genetic lesions could lead to retinal degeneration in man. The central preliminary findings leading to the proposal are those of circadian rhythmicity and light stimulation of disk shedding and of light stimulation of disk addition. The rationale is to analyze disk addition in relationship to the basic cell processes that are involved in outer segment turnover using experimental design which could potentially disrupt the integration of these processes. Thus, it is proposed to analyze disk addition in relationship to production and transport of membrane precursors, disk shedding, disk displacement, and mechanisms of disk assembly. The approach is cell biological and will use the tools of electron microscopy and autoradiography in both in vivo and in vitro preparations. In several instances these analytical techniques will be used in conjunction with in vitro treatments with drugs which have specific inhibitory actions on the processes studied (i.e., protein synthesis). Much of the proposal is unified by the hypothesis that membrane precursors are delivered to the outer segment in the form of vesicles which are used to support the process of disk assembly, and evaluation of this hypothesis is a primary objective of the research. Other objectives are to evaluate the extent to which photoreceptors are able to regulate their turnover activities under conditions that establish a "disk assembly-disk loss" imbalance, to evaluate a possible mechanism of light stimulation of disk assembly-disk loss" imbalance, to evaluate a possible mechanism of light stimulation of disk assembly and to evaluate the possibility that microtubules and/or microfilaments are involved in the mechanics of outer segment turnover.